To develop an effective drug for oral mucositis Background: Oral mucositis is a painful dose-limiting side effect of many forms of cancer radiation and chemotherapy. According to a recent report by the National Comprehensive Cancer Network, mucositis is the most significant adverse symptom of cancer therapy reported by patients. There is only a single medication approved for mucositis, and it is only used in a limited set of patients. There is a compelling need for new, more effective therapeutics to reduce the severe pain and morbidity associated with this serious condition. Avaxia is developing a topical polyclonal anti-TNF antibody therapeutic for oral mucositis. TNF is an inflammatory cytokine that is believed to play a central role in the development of mucositis. We hypothesize that anti-TNF antibody will shut down the inflammatory response;preliminary data demonstrate that topical application of a rabbit polyclonal anti-TNF antibody significantly reduced both the severity and duration of radiation-induced mucositis in hamsters. In this proposal, Avaxia is isolating anti- TNF antibody from the early milk (colostrum) of immunized cows. Bovine colostral antibodies have a long history of safe human exposure, making them ideal for delivery to the oral cavity. The goal of the work described in this SBIR phase I application is to evaluate the technical feasibility of treating radiation- induced oral mucositis with topical anti-TNF bovine colostral antibody. The specific aims are as follows: To test the activity of the anti-TNF antibody in vitro (SA#1). To test the activity of topically applied anti-TNF antibody in hamsters with radiation-induced oral mucosits (SA#2). To define the distribution of topically applied anti-TNF antibody in hamsters with oral mucositis (SA#3). If these studies are successful, the SBIR Phase II application will evaluate the antibody in fractionated radiation regimens that more closely mimic clinical radiation therapy. Together, these studies will define the commercial opportunity offered by the bovine antibody and will form the basis of the pre-clinical pharmacology package to be used in support of an IND filing. PUBLIC HEALTH RELEVANCE: Oral mucositis is a serious and painful dose-limiting side effect of many forms of cancer radiation and chemotherapy. The goal of the work described in this application is to evaluate the technical feasibility of treating radiation-induced oral mucositis with a topical antibody. The long term goal is the development of a safe and effective medication.